Unraveling the mystery: How bad is BAG3 in hematological malignancies?

Liu, Qinghan; Liu, Jinde; Huang, Xinyue

doi:10.1016/j.bbcan.2022.188781

Cited by 2 publications

(1 citation statement)

References 131 publications

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“…This means that the high-risk score often causes VEN-resistance by interacting with anti-apoptosis proteins, which is one of the main causes of VEN-resistance ( 9 , 69 , 70 ). Of other 5 senescence genes, as the co-variants of BCL-2 , BAG3 works together with BAG1 to maintain the viability of myeloid cells, dysregulation of which could lead to physiological abnormalities ( 71 ). Notably, previous studies have indicated that BAG3 is associated with a poor AML prognosis ( 72 ), and involved in resistance to chemotherapy ( 73 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia

Ke,

Xie,

et al. 2023

Front. Oncol.

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BackgroundSatisfactory responses can be obtained for acute myeloid leukemia (AML) treated by Venetoclax (VEN)-based therapy. However, there are still quite a few AML patients (AMLs) resistant to VEN, and it is critical to understand whether VEN-resistance is regulated by senescence.MethodsHere, we established and validated a signature for predicting AML prognosis based on VEN resistance-related senescence genes (VRSGs). In this study, 51 senescence genes were identified with VEN-resistance in AML. Using LASSO algorithms and multiple AML cohorts, a VEN-resistance senescence prognostic model (VRSP-M) was developed and validated based on 6-senescence genes.ResultsAccording to the median score of the signature, AMLs were classified into two subtypes. A worse prognosis and more adverse features occurred in the high-risk subtype, including older patients, non-de novo AML, poor cytogenetics, adverse risk of European LeukemiaNet (ELN) 2017 recommendation, and TP53 mutation. Patients in the high-risk subtype were mainly involved in monocyte differentiation, senescence, NADPH oxidases, and PD1 signaling pathway. The model’s risk score was significantly associated with VEN-resistance, immune features, and immunotherapy response in AML. In vitro, the IC50 values of ABT-199 (VEN) rose progressively with increasing expression of G6PD and BAG3 in AML cell lines.ConclusionsThe 6-senescence genes prognostic model has significant meaning for the prediction of VEN-resistance, guiding personalized molecularly targeted therapies, and improving AML prognosis.

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